Abstract |
1. GTx-024, a novel selective androgen receptor modulator, is currently being investigated as an oral treatment for muscle wasting disorders associated with cancer and other chronic conditions. 2. Absorption of GTx-024 was rapid and complete, with high oral bioavailability. A wide tissue distribution of [(14)C] GTx-024 derived radioactivity was observed. [(14)C] GTx-024-derived radioactivity had a moderate plasma clearance (117.7 and 74.5 mL/h/kg) and mean elimination half-life of 0.6 h and 16.4 h in male and female rats, respectively. 3. Fecal excretion was the predominant route of elimination, with ∼70% of total radioactivity recovered in feces and 21-25% in urine within 48 h. Feces of intact rats contained primarily unchanged [(14)C] GTx-024 (49.3-64.6%). Metabolites were identified in urine and feces resulting from oxidation of the cyanophenol ring (M8, 17.6%), hydrolysis and/or further conjugation of the amide moiety (M3, 8-12%) and the cyanophenol ring (M4, 1.3-1.5%), and glucuronidation of [(14)C] GTx-024 at the tertiary alcohol (M6, 3.5-3.7%). There was no quantifiable metabolite in plasma. 4. In summary, in the rat GTx-024 is completely absorbed, widely distributed, biotransformed through several metabolic pathways, and eliminated in feces primarily as an unchanged drug.
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Authors | Juhyun Kim, Ronghua Wang, Karen A Veverka, James T Dalton |
Journal | Xenobiotica; the fate of foreign compounds in biological systems
(Xenobiotica)
Vol. 43
Issue 11
Pg. 993-1009
(Nov 2013)
ISSN: 1366-5928 [Electronic] England |
PMID | 24074268
(Publication Type: Journal Article)
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Chemical References |
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Topics |
- Absorption
- Administration, Oral
- Amides
(chemistry, metabolism, pharmacokinetics, urine)
- Anilides
- Animals
- Autoradiography
- Biotransformation
- Feces
(chemistry)
- Female
- Male
- Mass Spectrometry
- Metabolomics
- Radioactivity
- Rats
- Rats, Long-Evans
- Rats, Sprague-Dawley
- Reference Standards
- Time Factors
- Tissue Distribution
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